title: Removal of 2-arachidonylglycerol by direct hemoperfusion therapy with polymyxin B immobilized fibers benefits patients with septic shock.
abstract: Arachidonylethanolamide (AEA) and 2-arachidonylglycerol (2-AG) are endocannabinoids involved in septic shock, and 8-epi prostaglandin F2alpha (F2-isoprostane) is a biomarker of oxidative stress in biological systems. Because the antibiotic polymyxin B absorbs endocannabinoids as well as endotoxins, direct hemoperfusion therapy with polymyxin B-immobilized fibers (PMX-DHP) decreases serum levels of endocannabinoids. To investigate the features of sepsis and determine the proper use of PMX-DHP, we measured the changes in levels of endocannabinoids and F2-isoprostane in patients with septic shock. Twenty-six patients with septic shock, including those with septic shock induced by peritonitis, underwent laparotomy for drainage. Endocannabinoids absorption with PMX-DHP was examined in two groups of patients: patients whose mean arterial blood pressure (mABP) had increased more than 20 mm Hg (responder group; N = 13); and patients iwhose mABP did not increase or had increased no more than 20 mm Hg (non-responder group; N = 13). Levels of AEA did not change after PMX-DHP in either the non-responder or responder groups, whereas levels of 2-AG decreased significantly after PMX-DHP in the responder group, but not in the non-responder group. F2-isoprostane gradually increased after PMX-DHP treatment; on the other hand, levels of F2-isoprostane remained constant in the responder group. Patients with septic shock are under considerable oxidative stress, and 2-AG plays an important role in the cardiovascular status of these patients. The removal of 2-AG by PMX-DHP benefits patients with septic shock by stabilizing cardiovascular status and decreasing long-term oxidative stress.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Jikei University School of Medicine, Tokyo, Japan. y.kase@jikei.ac.jp
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kase
authors.forename: Toru
authors.initials: T
authors.lastname: Obata
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Kenichi
authors.initials: K
authors.lastname: Iwai
authors.forename: Keita
authors.initials: K
authors.lastname: Saito
authors.forename: Keitaro
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Masanori
authors.initials: M
authors.lastname: Takinami
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Tanifuji
mesh_terms: D018806:APACHE; D000368:Aged; D001095:Arachidonic Acids / Q000097:blood*; D016022:Case-Control Studies; D063388:Endocannabinoids; D004731:Endotoxins / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006464:Hemoperfusion / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011112:Polymyxin B / Q000627:therapeutic use*; D053284:Polyunsaturated Alkamides / Q000097:blood*; D011336:Probability; D011446:Prospective Studies; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000097:blood / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D004731:Endotoxins; D053284:Polyunsaturated Alkamides; D011112:Polymyxin B; C078814:anandamide